crossing96/oncoscreening huggingface dataset:
Plasmacytoid carcinoma of the bladder: a urothelial carcinoma variant with a predilection for intraperitoneal spread.	PURPOSE: Bladder plasmacytoid carcinoma is an invasive urothelial carcinoma subtype that is emphasized for its morphological overlap with plasma cells and metastatic carcinoma. Our experience suggests frequent intraperitoneal spread that is not typical of conventional urothelial carcinoma. MATERIALS AND METHODS: We identified cases of plasmacytoid urothelial carcinoma diagnosed on radical cystectomy. Patient age, gender, American Joint Committee on Cancer (7th edition) stage, metastatic spread/recurrence sites and clinical disease status at last followup were recorded. RESULTS: A total of 10 male and 5 female patients 42 to 81 years old were identified. One tumor was pT2, 11 pT3 and 3 pT4. Six of 15 patients (40%) presented with lymph node metastasis and 5 (33%) had intraperitoneal metastasis at cystectomy. These initial sites of metastatic spread included the prerectal space, ovary and vagina, ovary and fallopian tube, bowel serosa, and omentum and bowel serosa in 1 case each. Three patients had subsequent metastasis involving the prerectal space, pleural fluid and small bowel serosa, and bowel serosa in 1 each. Eight patients had followup information available, including 3 who died of disease, 3 with disease and 2 with no evidence of disease. CONCLUSIONS: Of the patients 33% with the plasmacytoid variant of urothelial carcinoma presented with intraperitoneal disease spread and 20% had subsequent metastasis involving serosal surfaces. The possibility of noncontiguous intraperitoneal spread involving serosal surfaces should be recognized to ensure proper intraoperative staging and clinical followup for patients with plasmacytoid carcinoma.	bladder
Expression of TRAIL, DR4, and DR5 in bladder cancer: correlation with response to adjuvant therapy and implications of prognosis.	OBJECTIVES: To explore the interrelationship of human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors DR4 and DR5 expressions level with patient prognosis and the response to adjuvant therapy in bladder cancer, the synergism function that is between chemotherapy and TRAIL on apoptosis induction in tumor cells. METHODS: The expression of TRAIL, DR4, and DR5 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 229 bladder cancer patients who had undergone transurethral resection. RESULTS: Cytoplasmic TRAIL, DR4, and DR5 expressions were detected in 35%, 75.1%, and 74.2% of bladder cancer patients, respectively. Patients with bladder cancer with either high DR4 or DR5 expression had a significantly longer postoperative recurrence-free rate than those with low expression of both during the 10-year follow-up. Multivariate analysis revealed that the expression of DR4 (P < .001), DR5 (P < .001) and epirubicin therapy (P = .034) were independent prognostic indicators of bladder cancer. Furthermore, epirubicin therapy significantly improved recurrence-free rate for the patients with DR4-high (P = .006) or DR5-high (P = .042) tumor. CONCLUSIONS: The results of the present study have shown for the first time that a combination of DR4 and DR5 expression have significant value in predicting the prognosis of bladder cancer. In addition, patients with high expression of both DR4 and DR5 might benefit from epirubicin therapy.	bladder
Ras-related tumorigenesis is suppressed by BNIP3-mediated autophagy through inhibition of cell proliferation.	Autophagy plays diverse roles in Ras-related tumorigenesis. H-ras(val12) induces autophagy through multiple signaling pathways including Raf-1/ERK pathway, and various ERK downstream molecules of autophagy have been reported. In this study, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) is identified as a downstream transducer of the Ras/Raf/ERK signaling pathway to induce autophagy. BNIP3 was upregulated by H-ras(val12) at the transcriptional level to compete with Beclin 1 for binding with Bcl-2. H-ras(val12)-induced autophagy suppresses cell proliferation demonstrated both in vitro and in vivo by expression of ectopic BNIP3, Atg5, or interference RNA of BNIP3 (siBNIP3) and Atg5 (shAtg5) using mouse NIH3T3 and embryo fibroblast cells. H-ras(val12) induces different autophagic responses depending on the duration of Ras overexpression. After a short time (48 hours) of Ras overexpression, autophagy inhibits cell proliferation. In contrast, a longer time (2 weeks) of Ras overexpression, cell proliferation was enhanced by autophagy. Furthermore, overexpression of mutant Ras, BNIP3, and LC3-II was detected in bladder cancer T24 cells and the tumor parts of 75% of bladder cancer specimens indicating a positive correlation between autophagy and tumorigenesis. Taken together, our mouse model demonstrates a balance between BNIP3-mediated autophagy and H-ras(val12)-induced tumor formation and reveals that H-ras(val12) induces autophagy in a BNIP3-dependent manner, and the threshold of autophagy plays a decisive role in H-ras(val12)-induced tumorigenesis. Our findings combined with others' reports suggest a new therapeutic strategy against Ras-related tumorigenesis by negative or positive regulation of autophagic activity, which is determined by the level of autophagy and tumor progression stages.	bladder
[Nested variant of urothelial carcinoma of bladder : a case report].	A 58-year-old man visited our hospital with gross hematuria. Cystoscopy revealed a papillary tumor around the left ureteral orifice. Transurethral resection of bladder tumor (TUR-Bt) was performed and histopathological findings revealed a nested variant of urothelial carcinoma. Computed tomography (CT) revealed no involvement of other organs. Laparoscopic radical cystectomy and orthotopic neobladder substitution (Studer methods) were performed. The histopathological stage was pT3aN0M0. Adjuvant chemotherapy (gemcitabine + cisplatin) was performed. The patient is currently free from disease at five months after the surgery.	bladder
Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer.	BACKGROUND AND OBJECTIVE: High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. HMGB1 overexpression has been reported in a variety of human cancers. However, the clinical significance of HMGB1 expression in bladder cancer (BC) remains unclear. This study is aimed to investigate the correlations between HMGB1 expression and prognosis in patients with BC. METHODS: HMGB1 protein expression in 164 primary BC tissue specimens was analyzed by immunohistochemistry, and its association with clinicopathologic factors and prognosis was also analyzed. RESULTS: HMGB1 protein had high expression in 87 of 164 cases of BC (53%). HMGB1 overexpression was significantly associated with tumor grade (P < 0.001), and stage (P = 0.001). The Kaplan-Meier survival analysis demonstrated that HMGB1 expression was significantly associated with shorter disease-free survival and overall survival (both P < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with BC. CONCLUSIONS: HMGB1 might be a new molecular marker to predict the prognosis of patients with BC.	bladder
Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers.	Three common urological diseases are bladder cancer, urinary tract infection, and hematuria. Seventeen bladder cancer biomarkers were previously discovered using iTRAQ - these findings were verified by MRM-MS in this current study. Urine samples from 156 patients with hernia (n=57, control), bladder cancer (n=76), or urinary tract infection/hematuria (n=23) were collected and subjected to multiplexed LC-MRM/MS to determine the concentrations of 63 proteins that are normally considered to be plasma proteins, but which include proteins found in our earlier iTRAQ study. Sixty-five stable isotope-labeled standard proteotypic peptides were used as internal standards for 63 targeted proteins. Twelve proteins showed higher concentrations in the bladder cancer group than in the hernia and the urinary tract infection/hematuria groups, and thus represent potential urinary biomarkers for detection of bladder cancer. Prothrombin had the highest AUC (0.796), with 71.1% sensitivity and 75.0% specificity for differentiating bladder cancer (n=76) from non-cancerous (n=80) patients. The multiplexed MRM-MS data was used to generate a six-peptide marker panel. This six-peptide panel (afamin, adiponectin, complement C4 gamma chain, apolipoprotein A-II precursor, ceruloplasmin, and prothrombin) can discriminate bladder cancer subjects from non-cancerous subjects with an AUC of 0.814, with a 76.3% positive predictive value, and a 77.5% negative predictive value. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.	bladder
Acidic sphingomyelinase induced by electrophiles promotes proinflammatory cytokine production in human bladder carcinoma ECV-304 cells.	Electrophiles in environmental pollutants or cigarette smoke are high risk factors for various diseases caused by cell injuries such as apoptosis and inflammation. Here we show that electrophilic compounds such as diethyl malate (DEM), methyl mercury and cigarette smoke extracts significantly enhanced the expression of acidic sphingomyelinase (ASMase). ASMase activity and the amount of ceramide of DEM-treated cells were approximately 6 times and 4 times higher than these of non-treated cells, respectively. Moreover, we found that DEM pretreatment enhanced the production of IL-6 induced by TNF-α. Knockdown of ASMase attenuated the enhancement of TNF-α-dependent IL-6 production. On the other hand, enhancement of TNF-α-induced IL-6 production was observed in ASMase-overexpressing cells without DEM. Fractionation of the lipid raft revealed that the TNF receptor 1 (TNFR1) was migrated into the lipid raft in DEM-treated cells or ASMase-overexpressing cells. The TNF-α-induced IL-6 expression required the clustering of TNFR1 since IL-6 expression were decreased by the destruction of the lipid raft with filipin. These results demonstrated a new role for ASMase in the acceleration of the production of TNF-induced IL-6 as a pro-inflammatory cytokine and indicated that electrophiles could potentiate inflammation response by up-regulating of ASMase expression following formation of lipid rafts.	bladder
Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder.	What's known on the subject? and What does the study add? Steroid hormone receptor signals have been implicated in bladder tumourigenesis and tumour progression. The expression of androgen and/or oestrogen receptors has been assessed in bladder cancer, leading to conflicting data of expression levels and their relationship to histopathological characteristics of the tumours. We simultaneously analyze three receptors in non-neoplastic bladder tissues as well as in primary and metastatic bladder tumour specimens. Our data demonstrate that the expression status correlates with tumour grades/stages and patients' outcomes. OBJECTIVE: To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown conflicting results and the prognostic significance of their expression remains unclear. PATIENTS AND METHODS: We investigated the expression of AR, ERα and ERβ in 188 bladder tumour specimens, as well as matched 141 non-neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry. We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort. RESULTS: AR/ERα/ERβ was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours. Significantly lower expression of AR/ERα was found in high-grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low-grade tumours (55%; P= 0.0232/38%; P= 0.0483) and tumours not invading muscularis propria (51%; P= 0.0181/35%; P= 0.0139), respectively. Significantly higher expression of ERβ was found in high-grade tumours (58%) and tumours invading muscularis propria (67%) compared to low-grade tumours (29%; P= 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively. Kaplan-Meier and log-rank tests further showed that positivity of ERβ (but not AR or ERα) was associated with the recurrence of low-grade tumours (P= 0.0072); the progression of low-grade tumours (P= 0.0005), high-grade tumours not invading muscularis propria (P= 0.0020) and tumours invading muscularis propria (P= 0.0010); or disease-specific mortality in patients with tumours invading muscularis propria (P= 0.0073). CONCLUSIONS: Compared to benign bladders, a significant decrease in the expression of AR, ERα or ERβ in bladder cancer was seen. Loss of AR or ERα was strongly associated with higher grade/more invasive tumours, whereas ERβ expression was increased in high-grade/invasive tumours and predicted a worse prognosis.	bladder
Antitumor effects of bladder cancer-specific adenovirus carrying E1A-androgen receptor in bladder cancer.	The high frequency of recurrence and poor survival rate of bladder cancer demand exploration of novel strategies. Gene therapy via adenovirus has shown promising potential for the treatment of tumors. We constructed a bladder cancer-specific adenovirus carrying E1A-androgen receptor (AR) under the control of UPII promoter and prostate stem cell antigen enhancer (PSCAE), designated as Ad/PSCAE/UPII/E1A-AR, and investigated its antitumor effects in vitro and in vivo. We demonstrated that Ad/PSCAE/UPII/E1A-AR could be selectively replicated in bladder tumor cell lines (5637, BIU87, EJ and T24) when compared with control adenovirus Ad/PSCAE/UPII/Luc. However, there was no evidence of cytotoxicity for normal human bladder cell line SV-HUC-1 and hepatoma cell line SMMC7721. AR agonist R1881 could strengthen the oncolytic effect of Ad/PSCAE/UPII/E1A-AR in bladder cancer cells. In addition, we demonstrated that intratumoral injection of Ad/PSCAE/UPII/E1A-AR into established subcutaneous human EJ tumors in nude mice could significantly regress the growth of tumor and markedly prolong survival for tumor-bearing mice; on the other hand, saline-treated tumors continued to grow rapidly. Our studies indicate that Ad/PSCAE/UPII/E1A-AR could effectively treat bladder cancer in vitro and in vivo. Furthermore, our findings provide a promising therapeutic modality for the treatment of bladder cancer.	bladder
The NQO1 rs1800566 polymorphism and risk of bladder cancer: evidence from 6,169 subjects.	OBJECTIVE: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to proline- toserine amino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individually published studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize the possible association. METHODS: A systematic literature search up to August 27, 2012 was carried out in PubMed, EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs. C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixed- or random-effect models. RESULTS: We identified 12 case-control studies including 3,041 cases and 3,128 controls for the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and risk of bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, in the subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95% CI = 1.08-1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95% CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. CONCLUSIONS: The results suggest that NQO1 rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.	bladder
Chlorin-based photodynamic therapy enhances the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in bladder cancer cells.	BACKGROUND: Photodynamic therapy (PDT) is an attractive, emerging therapeutic procedure suitable for the treatment of non-muscle-invasive bladder cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that belongs to the TNF superfamily of cytokines. The ability of TRAIL to selectively induce apoptosis in cancer cells but not in normal cells promotes the development of TRAIL-based cancer therapy. However, many tumor cells are resistant to TRAIL-induced apoptosis. The purpose of the study was to overcome TRAIL-resistance in bladder cancer cells by photodynamic therapy (PDT). MATERIAL/METHODS: Three human bladder transitional cancer cell lines - T24, 647V and SW780 - were treated with TRAIL and/or chlorin-based PDT. The cytotoxicity was measured by MTT and LDH assays and apoptosis was detected using annexin V by flow cytometry. RESULTS: Our test confirmed that T24 and 647V bladder cancer cells are resistant to TRAIL, whereas SW780 cells are sensitive to TRAIL. Then we examined the cytotoxic and apoptotic effects of TRAIL in combination with chlorin e6-polyvinylpyrrolidone (Ce6-PVP)-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with a low dose of PDT significantly sensitizes bladder cancer cells to TRAIL-induced apoptosis. Chlorin-based PDT augments the effect of TRAIL on bladder cancer cells. CONCLUSIONS: PDT with Ce6-PVP photosensitizer enhances the cytotoxic and apoptotic effects of TRAIL on bladder cancer cells. The obtained results suggest that combined treatment by TRAIL and PDT may provide the basis for a new therapeutic approach to induce cell death in bladder cancer.	bladder
Conditional survival of patients with urothelial carcinoma of the urinary bladder treated with radical cystectomy.	AIM OF STUDY: To examine the impact of survival probability according to duration of survivorship following radical cystectomy (RC) in patients diagnosed with urothelial carcinoma of the urinary bladder (UCUB). METHODS: Overall, 4991 UCUB patients who underwent RC were abstracted. The cumulative survival estimates were used to generate conditional survival rates. Cox regression analyses were performed for prediction of cancer-specific mortality (CSM), according to duration of survivorship. RESULTS: The five-year CSM-free survival rate was 63.9% at RC, and increased to 71.0%, 77.5%, 81.7%, 85.9% and 86.3% in patients who survived ≥ 1, 2, 3, 4 and 5 years, respectively. Patients with pT2-4 disease benefitted from the highest increase in survivorship two years after RC. The same findings were recorded according to patients' nodal status. CONCLUSION: The survival of the first two years after RC markedly improves individual patient prognosis. The prognostic gains differ according to patient and tumour characteristics.	bladder
Functional polymorphisms in promoter survivin gene and its association with susceptibility to bladder cancer in North Indian cohort.	Survivin is a member of novel inhibitor of apoptosis protein family which expressed in human cancers. The molecular detection of bladder cancer by targeting Survivin as a novel marker may be useful in the occurrence and progression of cancer. We genotyped Survivin -31G>C, -1547A>G and -241C>T by PCR-restriction fragment length polymorphism to evaluate the risk of bladder cancer (BC) in 200 BC patients and 200 healthy controls from North Indian cohort. We observed significant increased BC risk associated with variant CC genotype of Survivin -31G>C having 2.6 fold risk. The variant genotype of Survivin -1547A>G was significantly associated with BC risk (P = 0.047). In case of Survivin -241C>T the protective genotype for BC was heterozygous (P = 0.035). Smoking significantly modulated the risk in patients with Survivin -1547A>G polymorphism. Variant as well as hetero genotype of Survivin -31G>C was associated with reduced risk of recurrence (HR = 0.22 and 0.35) in BC patients receiving BCG treatment thus showing least survival. Furthermore, the haplotype analysis revealed C-A-T haplotype to be associated with reduced BC risk. Our findings suggested that the functional polymorphism -31G>C, -1547A>G and -241C>T in the promoter of Survivin gene may play a significant role in mediating the BC risk among North Indian cohort.	bladder
High expression of polo-like kinase 1 is associated with the metastasis and recurrence in urothelial carcinoma of bladder.	OBJECTIVES: Polo-like kinase 1 (Plk1) has been widely pursued as an oncology target because it is overexpressed in several human tumor types. To investigate whether Plk1 plays a general role in bladder urothelial carcinoma, we examined the expression of Plk1 protein in bladder urothelial carcinoma and cell lines, and analyzed the relationship among Plk1 protein expression, metastasis, and recurrence of urinary bladder urothelial carcinoma. METHODS: Immunohistochemistry was used to detect the expression of Plk1 in 120 bladder urothelial carcinoma. Moreover, the expression of Plk1 was analyzed by Western blot in 60 bladder urothelial carcinoma and 21 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of scytonemin (the inhibitor of Plk1). Statistical analysis was used to discuss the association between Plk1 expression and clinicopathologic parameters, tumor metastasis and recurrence, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells. RESULTS: There was a significantly higher Plk1expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Plk1 expression was positively correlated with histologic grade, pT stage, recurrence, and metastasis. With the increasing concentration of scytonemin, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage. CONCLUSION: Plk1 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Plk1 played an important function on the bladder cancer cells' proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer.	bladder